Approximately one out of four medically ill patients have depression, and the prevalence is projected to increase during the twenty-first century. Depression independently predicts mortality and considerable evidence suggests that depression may increase risk through lowering parasympathetic (PSNS) control of the heart and increasing sympathetic nervous system (SNS) activity. Depression may be especially harmful following an acute myocardial infarction (MI), where clinical depression is associated with a 2- to 4-fold increase in mortality. In the acute phase following an MI, there is a transient denervation of the PSNS and a marked increase in SNS activity. During this period, low PSNS control and high SNS activity are strongly predictive of subsequent fatal cardiac events. Because depression itself is associated with reduced PSNS and increased SNS activity, the presence of depression may exacerbate the impaired PSNS control and increased SNS activity observed after an MI. The purpose of this study is twofold: (1) to examine the effects of depression on PSNS control and SNS activity after MI; and (2) to examine the biobehavioral pathways involved in the altered PSNS and SNS control associated with depression by evaluating the contribution of anxiety, physical activity, and medical comorbidity to this relationship. The effects of depression, anxiety, physical activity, and medical comorbidity on PSNS and SNS control and recovery will be determined in 360 post-MI patients, assessed at two weeks, six weeks, and thirteen weeks post-MI. At the time of each assessment, depression will be measured using a diagnostic interview and anxiety will be measured using the Spielberger state-trait anxiety inventory. SNS activity will be determined by the excretion of urinary catecholamines over 24-hours, and PSNS control will be measured from baroreflex sensitivity and 24-hour heart rate variability; each of these measures are prognostic of mortality. Physical activity will be estimated using 24-hour wrist actigraphy. We believe that the study findings will further our understanding of the biobehavioral pathways that link depression to altered autonomic nervous system control, and provide the basis for developing evidence-based treatment programs to improve prognosis in depressed patients.